Enhancer transcription profiling reveals an enhancer RNA-driven ferroptosis and new therapeutic opportunities in prostate cancer.

Enhancer RNAs (eRNAs), a subclass of non-coding RNAs transcribed from enhancer regions, have emerged as critical regulators of gene expression; however, their functional roles in prostate cancer remain largely unexplored. In this study, we performed integrated chromatin accessibility and transcriptomic analyses using ATAC-seq and RNA-seq on twenty pairs of prostate cancer and matched benign tissues. By incorporating chromatin immunoprecipitation sequencing data, we identified a subset of differentially expressed eRNAs significantly associated with genes involved in prostate development and oncogenic signaling pathways.

Impact of parental myopia on myopia in schoolchildren and adolescents in China: A national cross-sectional survey.

Background: Parental myopia is an important risk factor for myopia in Chinese children and adolescents. This study aimed to assess the influence of parental myopia and the severity of myopia on offspring and to evaluate whether adopting healthy lifestyles can mitigate the effects of parental myopia on offspring.

Methods: This cross-sectional study analyzed data from children and adolescents aged 6-17 years with complete vision assessments and parental history of myopia from six provinces in China during 2013-2014.

Polydopamine-based nano-protectant for prolonged boar semen preservation by eliminating ROS and regulating protein phosphorylation via D2DR-mediated cAMP/PKA signaling pathway.

Preservation of porcine semen is essential for artificial insemination and genetic improvement in pig breeding programs. However, the overproduction of reactive oxygen species (ROS) and lower levels of protein phosphorylation emerge as two challenges during semen preservation. Inspired by the innate ligand-receptor binding biofunction of dopamine, herein, a dual-task nano-protectant that combines ROS-scavenging and protein phosphorylation-regulating properties via incorporating the natural antioxidant epigallocatechin gallate (EGCG) into polydopamine nanoparticles (EGCG@PDA NPs) was proposed to enhance the quality of pig semen during storage at 4 ℃.

Investigation of absorption, metabolism, and excretion of [C]pruxelutamide (GT0918), an androgen receptor antagonist in humans.

Aims: The primary objective of this study was to determine the pharmacokinetics, mass balance and biotransformation of [C]GT0918 in humans after the drug was administered to healthy Chinese male subjects.

Methods: The absorption, metabolism, and excretion (AME) of GT0918 was characterized via isotope labelling technology in six healthy Chinese male subjects after receiving a single 200 mg oral dose of [C]GT0918 (80 μCi), and the phenotype, together with the metabolic mechanism of GT0918, was confirmed in vitro.

Results: The medium T of total radioactivity was 6.

Ultrasound-laccase pre-treatment enhances agarwood essential oil extraction and bioactivity.

Agarwood essential oil is prized for its elegant aroma and pharmacological properties; however, the traditional hydrodistillation method suffers from inefficiencies, constraining the industrial potential of agarwood. We proposed an ultrasonic-assisted laccase synergistic pretreatment technique that enhanced extraction throughput by 70.90 % compared to the traditional method by facilitating pore formation in agarwood and expediting the release of essential oil.

Maternal Exposure to Polystyrene Nanoplastics Disrupts Spermatogenesis in Mouse Offspring by Inducing Overexpression in Undifferentiated Spermatogonia.

Undifferentiated spermatogonia (Undiff-SPG) plays a critical role in maintaining continual spermatogenesis. However, the toxic effects and molecular mechanisms of maternal exposure to nanoplastics on offspring Undiff-SPG remain elusive. Here, we utilized a multiomics combined cytomorphological approach to explore the reproductive toxicity and mechanisms of polystyrene nanoplastics (PS-NPs) on offspring Undiff-SPG in mice after maternal exposure.

Tuning Surface Valences of Nanoengagers to Enhance Their Structural Advantages for Efficiently Redirecting T Cells against Solid Tumors.

The nanoengager strategy, which enhances receptor signaling responsiveness through a multivalent ligand binding mode, offers a promising approach for improving immune cell redirecting therapy. Increasing nanomaterial platforms have been developed for constructing more flexible and multifunctional nanoengagers, but the different mediating mechanisms from their multivalent nanostructures, compared to original monomolecule engagers, have rarely been discussed. Here, we constructed dual-specificity T cell nanoengagers (TNEs) targeting CD3 and PDL1 receptors based on a polyethylene glycol--polylactic acid (PEG--PLA)-assembled nanoparticle and specifically studied the impact of surface antibody valences on their functional mechanisms, thereby enhancing the structural advantages of TNEs against solid tumors.

Beneficial effects of EGCG on boar sperm quality during liquid storage at 4 °C are mediated by DRD2 receptor.

Epigallocatechin gallate (EGCG), a natural antioxidant, plays a vital role in modulating sperm function, yet its protective impact on boar spermatozoa during liquid preservation at 4 °C remains elusive. This study aimed to investigate the beneficial effects of EGCG on boar semen preservation, and elucidate the potential mechanism. Multiple parameters including sperm quality, anti-oxidative status, protein phosphorylation levels, membrane receptor and cyclic adenosine monophosphate/protein kinase A (cAMP/PKA) signaling pathways were analyzed using computer-assisted semen analysis system, Western blot and molecular docking techniques.

Absorption, metabolism, and excretion of oral [C] radiolabeled donafenib: an open-label, phase I, single-dose study in humans.

Purpose: The study aims to investigate the absorption, metabolism, and excretion of donafenib, a deuterated derivative of sorafenib, in healthy Chinese male volunteers.

Methods: Six healthy Chinese male volunteers were administered a single oral dose of 300 mg donafenib containing 120 µCi of [14 C]-donafenib. The study involved collecting and analyzing plasma, urine, and feces samples to determine the recovery and distribution of total radioactivity, identify metabolites, and assess the metabolic pathways of donafenib.

Polymeric immunogel prevents tumor recurrence and metastasis by dual activation of innate and adaptive immunity.

Tumor recurrence and metastasis after surgery are important factors affecting patient survival. The immunosuppressed tumor microenvironment after surgery reduces the ability of the immune system to clear residual tumor cells, thus increasing the risk of recurrence and metastasis. Currently, immunotherapy-based adjuvant therapy can effectively inhibit tumor recurrence and metastasis after surgery, but simultaneous and efficient synergistic activation of adaptive and innate immunity is a challenge.

Development and validation of a comprehensive predictive model for surgical planning in patients with renal cell carcinoma and inferior vena cava tumor thrombus.

Objective: To investigate preoperative predictors for selecting different surgical approaches in patients with renal cell carcinoma with inferior vena cava (IVC) tumor thrombus (RCC-IVCTT), and to establish and validate corresponding predictive models.

Methods: Clinical data of 583 RCC-IVCTT patients were retrospectively analyzed. Of these, 465 cases were used to construct predictive models, and 118 cases were used for validation.

Clinical pharmacokinetic characteristics of Jaktinib in subjects with hepatic impairment in a phase I trial.

Jaktinib is a novel Janus kinase (JAK) inhibitor, and a phase I clinical trial of single-dose Jaktinib was conducted in a population of subjects with hepatic impairment to assess the safety, tolerability, and pharmacokinetic characteristics of Jaktinib. The patients were administered orally with 100 mg Jaktinib on day 1 in all the mild hepatic impairment group (mild group, n = 8), moderate hepatic impairment group (moderate group, n = 8) and normal hepatic function group (normal group, n = 8), and the blood samples were collected for later analysis. The mild to moderate hepatic impairment affected the metabolism of Jaktinib, which may lead to accumulation of original Jaktinib.

Estimating the global and regional burden of lower respiratory infections attributable to leading pathogens and the protective effectiveness of immunization programs.

Objectives: Reducing mortality from infectious diseases is an urgent global public health priority. Streptococcus pneumoniae, H. influenzae, and influenza virus are the three leading causes of lower respiratory infections (LRIs) death worldwide.

Trojan-Horse Strategy Targeting the Gut-Liver Axis Modulates Gut Microbiome and Reshapes Microenvironment for Orthotopic Hepatocellular Carcinoma Therapy.

Reversing the hepatic inflammatory and immunosuppressive microenvironment caused by gut microbiota-derived lipopolysaccharides (LPS), accumulating to the liver through the gut-liver axis, is crucial for suppressing hepatocellular carcinoma (HCC) and metastasis. However, synergistically manipulating LPS-induced inflammation and gut microbiota remains a daunting task. Herein, a Trojan-horse strategy is proposed using an oral dextran-carbenoxolone (DEX-CBX) conjugate, which combines prebiotic and glycyrrhetinic acid (GA) homologs, to targeted delivery GA to HCC through the gut-liver axis for simultaneous modulation of hepatic inflammation and gut microbiota.

ATF3 as a response factor to regulate Cd-induced reproductive damage by activating the NRF2/HO-1 ferroptosis pathway.

Cadmium (Cd) has garnered significant attention due to reproductive toxicity in inducing ferroptosis. However, the specific mechanisms underlying Cd-induced germ cell ferroptosis remain poorly understood. This study aimed to systematically explore the molecular mechanisms of germ cell ferroptosis by investigating differential changes in transcription factors and proteins in male mice treated orally with CdCl (0.

Analysis and functional validations of multiple cell death patterns for prognosis in prostate cancer.

Prostate cancer (PCa) has garnered significant attention due to its rising incidence, variable therapeutic outcomes, and the absence of reliable prognostic markers. The significance of different cell death patterns in tumor development underscores their potential as predictors of PCa prognosis. This study utilized The Cancer Genome Atlas (TCGA) datasets to evaluate the prognostic capabilities of 15 cell death patterns and established a Cell Death Index (CDI) signature based on necrosis and cuproptosis-related genes.

PDIA2 is associated with the prognosis of prostate cancer, and downregulation of PDIA2 delays the progression of prostate cancer cells.

Protein Disulfide-Isomerase A2 (PDIA2) is a gene that encodes proteins, responsible for protein folding and modification within cells. The development and course of many disorders are intimately linked to the aberrant expression of PDIA2. Nevertheless, more research is necessary to fully understand PDIA2's biological significance in pan-cancer, notably in prostate cancer (PCa).

Burden of cardiovascular disease among the Western Pacific region and its association with human resources for health, 1990-2021: a systematic analysis of the Global Burden of Disease Study 2021.

Background: A comprehensive profile of cardiovascular disease (CVD) burden and human resources for health (HRH) distribution in the WHO Western Pacific region has yet to be presented. Studies on the relationship between HRH and CVD in this region are limited. We aimed to describe CVD trends and HRH density in the Western Pacific region and explore the association of HRH with CVD burden.

Pharmacokinetics, Mass Balance, and Biotransformation of [C]tinengotinib, A Novel Multi-target Kinase Inhibitor, in Healthy Subjects.

Background And Objective: Tinengotinib, a novel multi-target small molecule kinase inhibitor, is currently undergoing phase II clinical trial in the USA and China. The purpose of this open-label study was to investigate the absorption, metabolism, and excretion of [C]tinengotinib following a single oral dose in healthy subjects.

Methods: Six healthy male subjects received a single oral dose of [C]tinengotinib capsules at 10 mg/100 µCi, and blood, urine, and feces samples were collected.

Maternal exposure to ambient ozone and fetal congenital heart defects: a national multicenter study in China.

Background: Ambient O has demonstrated an aggravated increasing trend in the context of global warming. The available evidence of maternal exposure to ambient O on fetal congenital heart defects (CHD) is still limited, especially in high polluted areas.

Objective: To examine associations of maternal exposure to ambient O during early pregnancy with fetal CHDs.

Comparison of the efficacy and safety of unilateral and bilateral approach kyphoplasty in the treatment of osteoporotic vertebral compression fractures: A meta-analysis.

Objectives: The study aimed to compare the efficacy and safety of unilateral versus bilateral percutaneous kyphoplasty (PKP) in treating osteoporotic vertebral compression fractures.

Materials And Methods: Adhering to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, three English-language databases were systematically reviewed: PubMed, Web of Science, and the National Library of Medicine. The search was conducted between their inception and January 1, 2023.

Minimally Invasive Injectable Gel for Local Immunotherapy of Liver and Gastric Cancer.

Local immunotherapy represents a promising solution for preventing tumor recurrence and metastasis post tumor surgical resection by eliminating residue tumor cells as well as eliciting tumor-specific immune responses. Minimally invasive surgery has become a mainstream surgical method worldwide due to its advantages of aesthetics and rapid postoperative recovery. Unfortunately, the currently reported local immunotherapy strategies are mostly designed to be used after open laparotomy, which go against the current surgical philosophy of minimally invasive therapy and is not suitable for clinical translation.

Uniform Polymeric Nanovaccine Platform for Improving the Availability and Efficacy of Neoantigen Peptides.

Personalized cancer vaccines targeting specific neoantigens have been envisioned as one of the most promising approaches in cancer immunotherapy. However, the physicochemical variability of the identified neoantigens limits their efficacy as well as vaccine manufacturing in a uniform format. Herein, we developed a uniform nanovaccine platform based on poly(2-oxazoline)s (POx) to chemically conjugate neoantigen peptides, regardless of their physicochemical properties.